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		<h2 class="subtitle">Understanding Molecular Profiling</h2>
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<article class="content widget expert-content" itemprop="articleBody">
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	<p class="mrb">
			<span class="published">
				Updated August 02, 2014.
			</span>
            <br><br>Written or reviewed by a board-certified physician. See About.com's <a href="http://www.about.com/health/review.htm">Medical Review Board</a>.
	</p>
				<div class="firstBlock"><p><span>One of the most exciting advances in the treatment of lung cancer has come from an understanding of genetic changes in lung cancer cells.&nbsp; Whereas in the past we broke lung cancers down into perhaps 5 <a href="/od/typesoflungcancer/a/lungcancertypes.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="1">types,</a> we now know that no two lung cancers are the same.&nbsp; If there were 30 people in a room with lung cancer, they would have 30 different and unique types of lung cancer.</span></p></div>


				<p>If you’ve been recently diagnosed with lung cancer, especially <a href="/od/typesoflungcancer/a/Lung-Adenocarcinoma.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="2">lung adenocarcinoma</a>, your oncologist may have talked to you about genetic testing (otherwise known as molecular profiling or biomarker testing) of your tumor. &nbsp;It's now recommended that all lung cancer patients with advanced or metastatic&nbsp;lung adenocarcinoma (a type of non-small cell lung cancer) have biomarker testing to look for EGFR mutations and ALK rearrangements. &nbsp;In addition,&nbsp;patients with other forms of non-small cell lung cancer (for example, adenosquamous carcinoma in non-smokers) should also be considered for testing.&nbsp;&nbsp;What does this mean?</p>


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				<h3><strong>What is Genetic Testing (Molecular Profiling) of a Lung Cancer Tumor?</strong></h3>


				<p>Genetic testing involves&nbsp;tests that a pathologist performs in the lab using a sample of your cancer tissue - tests that look at the cancer from a <em><strong>molecular</strong></em> level.&nbsp; This&nbsp;tissue may come from a <a href="/od/Lung-Nodules-and-Masses/a/Lung-Biopsy.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="3">biopsy</a> of your tumor, or from tissue removed during&nbsp;<a href="/od/treatmentoflungcancer/a/lungcancersurg.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="4">surgery for lung cancer</a>.&nbsp; The reason behind this is that&nbsp;cancers have gene mutations that &quot;drive&quot; or control the growth of the cancer. &nbsp;Simplistically, if these mutations can be identified, then treatments can be used&nbsp;which &quot;target&quot; these mutations, hence&nbsp;stopping&nbsp;the&nbsp;growth of the cancer. &nbsp;It is these mutations that lead to the development of a cancer in the first place.&nbsp;</p>


				<p>Before going further it's&nbsp;helpful to address something that is confusing for many people.&nbsp; There are two primary types of <a href="http://biology.about.com/od/basicgenetics/ss/gene-mutation.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="5">gene mutations</a>. &nbsp;<span>&nbsp;</span></p>


				<h3><strong>Hereditary Mutations vs Aquired Mutations in Cancer</strong></h3>


				<p>One type of mutations are &nbsp;<strong><em>hereditary mutations (also called germline mutations</em></strong>,) meaning you inherit genes with mutations from one or more parents.&nbsp; Common examples of these mutations include <a href="http://menshealth.about.com/cs/genetics/a/hemophilia.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="6">hemophilia</a>&nbsp;associated as well as mutations that may predispose someone to developing breast cancer (<a href="http://breastcancer.about.com/od/breastcancerglossary/g/brca1.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="7">BRCA1</a> and <a href="http://breastcancer.about.com/od/breastcancerglossary/g/brca2.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="8">BRCA2 </a>mutations.)</p>


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				<p>The type of mutations that scientists look&nbsp;for in people with lung cancer are instead called <strong><em>acquired mutations (also called somatic mutations.) &nbsp;</em></strong>These mutations are <strong>not </strong>present at birth (they do not run in families) but rather develop in the process of cells becoming cancerous.</p>


						<ul> 
 
							<li><a href="/od/Biology-of-Cancer/a/Cancer-Cells.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="9">What are Cancer Cells?</a></li> 
 
							<li><a href="/od/Biology-of-Cancer/a/Cancer-Cells-Normal-Cells.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="10">Cancer Cells vs Normal Cells</a></li> 
</ul>


				<h3><strong>What Exactly are Gene Mutations?</strong></h3>


				<p>Gene mutations are changes to a particular gene in a&nbsp;<a href="http://biology.about.com/od/geneticsglossary/g/chromosome.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="11">chromosome</a>.&nbsp; All genes are made up of variable sequences of 4 amino acids (called bases); adenine, tyrosine, cytosine, and guanine.&nbsp; When a gene is exposed to toxins&nbsp;in the environment, or when an accident occurs in cell division, a mutation (change) may occur. In some cases it may mean that one base is substituted&nbsp;for another, say adenine instead of guanine.&nbsp; In other cases bases may be inserted, or deleted, or genes may be rearranged in some way.</p>


						<ul> 
 
							<li><a href="http://biology.about.com/od/genetics/ss/genetic-code.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="12">The Genetic Code</a></li> 
</ul>


				<h3><strong>Significance of Gene Mutations</strong></h3>


				<p>Why are oncologists interested in acquired gene mutations in a tumor?&nbsp; First, we should&nbsp;talk about the two types of acquired mutations found in lung cancers.&nbsp; One type of mutation is termed a <strong><em>driver mutation</em></strong>.&nbsp; These mutations, via&nbsp;several mechanisms, “drive” the growth of a tumor.&nbsp; In lung cancer the number of driver mutations is variable.&nbsp; In one study, an average of 11 driver mutations per cancer were found.&nbsp;&nbsp;Another type of mutation is termed a <strong><em>passenger mutation</em></strong>.&nbsp; Just as someone may be a passenger in a car, these genes do not drive the cancer and are basically along for the ride.&nbsp; Again we don’t know exactly how many passenger mutations are present in a tumor (and the number varies from tumor to tumor) but some tumors may have more than 1,000 of these mutations.&nbsp;</p>


				<p>Driver mutations not only initiate the development of a cancer, but work to maintain the growth of a cancer as well. &nbsp;</p>


				<h3><strong>Common Driver Mutations Found in Lung Cancer Tumors</strong></h3>


				<p>There are many mutations that are being studied by scientists looking at lung tumors. &nbsp;So far driver mutations have been&nbsp;identified in&nbsp;approximately 60%&nbsp;of lung adenocarcinomas.&nbsp; Researchers are now finding driver mutations in&nbsp;squamous cell lung cancer as well.</p>


				<p>Common driver mutations in lung cancer include (for starters):</p>


						<ul> 
 
							<li>EGFR mutations</li> 
 
							<li>KRAS mutations</li> 
 
							<li>EML4-ALK Rearrangements</li> 
 
							<li>MET mutation</li> 
</ul>


				<p>These 4 mutations are in general mutually exclusive and are only rarely seen in the same tumor.</p>


				<h3><strong>Personalized Treatments Available Based on Genetic Testing</strong></h3>


				<p>The use of &quot;targeted therapies&quot; - that is medications that target particular genetic abnormalities in a tumor -- has been coined <a href="http://patients.about.com/od/yourdiagnosis/a/persmedicine.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="13">personalized medicine</a>. &nbsp;What this means is that rather than a conventional chemotherapy drug that attacks all rapidly dividing cells, a targeted drug instead attacks a particular abnormality present only in your&nbsp;cancer cells. &nbsp;In general targeted treatments have fewer side effects than traditional chemotherapy. &nbsp;To date, targeted therapies that have been approved for people with lung cancer include:</p>


						<ul> 
 
							<li> <span>&nbsp;</span><a href="http://www.cancer.gov/cancertopics/druginfo/fda-erlotinib-hydrochloride" zt="-o1/XJ" target="_blank" data-component="link" data-source="inlineLink" data-type="externalLink" data-ordinal="14">Tarceva (erlotonib)</a><span>&nbsp;has been&nbsp;approved&nbsp;</span>for people whose tumor&nbsp;has an&nbsp;EGFR mutation (note: there are different&nbsp;types of EGFR mutations and not all of them are equally responsive to Tarceva)</li> 
 
							<li>&nbsp;<a href="http://www.cancer.gov/cancertopics/druginfo/fda-crizotinib" zt="-o1/XJ" target="_blank" data-component="link" data-source="inlineLink" data-type="externalLink" data-ordinal="15">Xalkori (crizotonib)</a>&nbsp;was approved by the FDA in 2011 for people whose tumor has an ALK4-EML gene rearrangement</li> 
</ul>


				<p><span>Other medications are being studied in clinical trials, including targeted therapies for those whose tumor becomes resistant to Tarceva or Xalkori..</span></p>


						<ul> 
 
							<li><a href="/od/Targeted-Therapy-Lung-Cancer/a/ALK-Lung-Cancer.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="16">More About ALK Positive Lung Cancer</a></li> 
</ul>


				<h3><strong>Resistance to Treatment</strong></h3>


				<p>A challenging&nbsp;problem with current targeted&nbsp;treatments&nbsp;is that nearly everyone inevitably becomes resistant to treatments we have.&nbsp; There are many mechanisms by which this occurs making it difficult to find one solution.&nbsp; Research is ongoing in clinical trials; evaluating both the use of substituting a second drug to target the mutations, and drugs that use different targets or mechanisms to attack the cancer cell.</p>


				<h3><strong>The Future</strong></h3>


				<p>The ability to understand the molecular profile of&nbsp;lung tumors is an extremely exciting area of research, and it’s likely that new treatments for other mutations&nbsp;will soon be available. &nbsp;An&nbsp;example of how rapidly this area of medicine is advancing is the ALK4-EML&nbsp;gene rearrangment. &nbsp;This gene &quot;mutation&quot; (actually a rearranglement) was discovered as recently as 2007. &nbsp;Through a rapid process, the medication Xalkori (crizotinib)&nbsp;was approved in 2011 for general use by the FDA for those patients whose tumors have this rearrangment. &nbsp;There are clinical trials currently in progress evaluating the use of second generation drugs for those who have become resistant to Xalkori.&nbsp;</p>


				<h3><strong>Next Step</strong></h3>


				<p>If you have been diagnosed with non-small cell lung cancer, especially lung adenocarcinoma or squamous cell lung cancer, talk to your doctor about genetic testing. &nbsp;<em><strong>Although testing is now recommended for everyone with advanced non-small cell lung cancer, a recent study reported that only 60% of oncologists are currently ordering testing.</strong></em> &nbsp;You may also wish to talk to your doctor about clinical trials that may be an option for you. &nbsp;If you are interested in looking into trials evaluating these treatments worldwide, check out the&nbsp;article below on how to find clinical trials. &nbsp;It can be confusing as you check out these databases, but help is near. &nbsp;Recently a <a href="/gi/o.htm?zi=1/XJ&amp;zTi=1&amp;sdn=lungcancer&amp;cdn=health&amp;tm=332&amp;f=22&amp;su=p284.13.342.ip_p1026.33.342.ip_&amp;tt=2&amp;bt=7&amp;bts=45&amp;zu=http%3A//www.emergingmed.com/networks/NationalLungCancerPartnership/" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="17">lung cancer clinical trial matching service</a> backed by several lung cancer organizations has become available. &nbsp;With this free service a trained nurse navigator can help you locate any clinical trials that may be an option for you.&nbsp;</p>


						<ul> 
 
							<li><a href="/od/treatmentoflungcancer/a/findingtrials.htm" data-component="link" data-source="inlineLink" data-type="internalLink" data-ordinal="18">Finding Clinical Trials for Lung Cancer Treatment</a></li> 
</ul>


				<p><sub>Sources:</sub></p>


				<p><sub>Hensing, T., Chawla, A., Batra, R., and R. Salgia. <a href="http://www.ncbi.nlm.nih.gov/pubmed/24292963" zt="-o1/XJ" target="_blank" data-component="link" data-source="inlineLink" data-type="externalLink" data-ordinal="19">A personalized treatment for lung cancer: molecular pathways, targeted therapies, and genomic characterization</a>. <em>Advances in Experimental Medicine and Biology</em>. 2014. 799:85-117.</sub></p>


				<p><sub>Kim, H., Mitsudomi, T., Soo, R., and B. Cho. <a href="http://www.ncbi.nlm.nih.gov/pubmed/23489560" zt="-o1/XJ" target="_blank" data-component="link" data-source="inlineLink" data-type="externalLink" data-ordinal="20">Personalized therapy on the horizon for squamous cell carcinoma of the lung</a>. <em>Lung Cancer</em>. 2013. 80(3):249-55.</sub></p>


				<p><sub>Li, T., Kung, H., Mack, P., and D. Gandara. <a href="http://www.ncbi.nlm.nih.gov/pubmed/23401433" zt="-o1/XJ" target="_blank" data-component="link" data-source="inlineLink" data-type="externalLink" data-ordinal="21">Genotyping and genomic profiling of non-small-cell lung cancer: implications for current and future therapies</a>. <em>Journal of Clinical Oncology</em>. 2013. 31(8):1039-49.</sub></p>


				<p><sub>Luo, S., and D. Lam. <a href="http://download.springer.com/static/pdf/13/art%253A10.1186%252F2213-0802-1-6.pdf?auth66=1388937150_8b6e5a9e42936c0aab9a23f464df0675&amp;ext=.pdf" zt="-o1/XJ" target="_blank" data-component="link" data-source="inlineLink" data-type="externalLink" data-ordinal="22">Oncogenic driver mutations in lung cancer</a>. <em>Translational Respiratory Medicine</em>. 2013. 1:6.</sub></p>


				<p><sub>Villaruz, L., Burns, T., Ramfidis, V., and M. Socinski. <a href="http://www.ncbi.nlm.nih.gov/pubmed/24258572" zt="-o1/XJ" target="_blank" data-component="link" data-source="inlineLink" data-type="externalLink" data-ordinal="23">Personalizing therapy in advanced non-small cell lung cancer</a>. <em>Seminars in Respiratory and Critical Care Medicine</em>. 2013. 34(6):822-36.</sub></p>



		
		

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